Urine Biomarkers of Benzene Metabolism: an Example of "Exposure Biology"

Martyn T. Smith, Ph.D., University of California Berkeley and Stephen M. Rappaport, Ph.D., University of North Carolina Chapel Hill
R01ES06721, P42ES04705, P30ES01896, P$2ES05948, and P30ES10126

Background: The recently released strategic plan for NIEHS entitled "New Frontiers in Environmental Sciences and Human Health" describes the need for an initiative on Exposure Biology that will "Develop sensitive markers of environmental exposure, early (pre-clinical) biological response, and genetic susceptibility." An example of this area of research can be found in studies done on benzene metabolism by NIEHS-supported investigators at the Schools of Public Health at the University of California Berkeley and the University of North Carolina Chapel Hill.

Benzene is a highly used and important industrial solvent and precursor in the production of plastics, synthetic rubber, dyes, drugs, etc. It is a natural constituent of crude oil, is highly volatile and is a known carcinogen. Benzene is highly toxic to the hematopoietic system and is a known cause of leukemia. Occupational exposures to benzene at air levels greater than 10 parts per million (ppm) have been linked to hematotoxicity, but recent reports have raised concerns about the health effects at levels below 1 ppm.

Advance: The researchers wanted to determine the usefulness of urinary metabolites of benzene as biomarkers of exposure in exposed and control subjects to define dose-related patterns of benzene metabolism. Their goal was to see if differences in dose led to differences in the pattern of metabolite levels. In a population of occupationally exposed Chinese-workers and controls, they found that at lower exposures (less than 1 ppm), the metabolism of benzene shifted towards its more toxic metabolites, hydroquinone and muconic acid.

Implications: This analysis identifies useful ranges of the various metabolites as biomarkers of benzene exposure. The researchers are conducting additional analyses to examine the dose-related metabolism of benzene and explore physiological and genetic factors that might influence metabolism and risk of disease. This research is a clear example of work that may lead to the ability to quantify individual exposures and to identify features that account for differing responses to the same exposure.

Citation: Kim S, Vermeulen R, Waidyanatha S, Johnson BA, Lan Q, Rothman N, Smith MT, Zhang L, Li G, Shen M, Yin S, Rappaport SM. Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism. Carcinogenesis. 2006 Apr;27(4):772-81.